New Insights in blaKPC Gene Mobilization in Pseudomonas aeruginosa: Acquisition of blaKPC-3 and Identification of a New Tn2-like NTE Mobilizing blaKPC-2

Abstract

Carbapenem-resistant Pseudomonas aeruginosa is a major cause of healthcare associated infections in hospitalized patients and what is more warring with reduced therapeutic options. The KPC is a powerful enzyme capable of hydrolyzing the carbapenems, described first in Klebsiella pneumoniae and it already has found in P. aeruginosa. Objective: To perform a comparative genomic analysis of two new genetic platforms mobilizing the blaKPC-2 and blaKPC-3 in two ST111 and ST235 pandemic clones of P. aeruginosa in Colombia, South America. Methods: Sixty-six blaKPC-harboring P. aeruginosa isolates were identified and characterized during a prospective study conducted in six high complex hospitals in Colombia. Genetic platforms mobilizing the blaKPC were analyzed. Results: The blaKPC-2 and blaKPC-3 were identified in 24 and 42 isolates, respectively. The blaKPC-2-harboring isolates belonged to ST235 and blaKPC-3 to ST111. The whole genome sequencing indicated that the blaKPC-3 gene was mobilized by the Tn4401b within a 55-kb-size environmental origin plasmid, which, in other isolates, was inserted into the chromosome through a transposition event of ISPa38. Regarding the blaKPC-2 gene, this was mobilized by a new Non-Tn4401 Element (NTE) derived from transposon Tn2 (proposed as variant IIg), which has been transposed into a 43-Kb-size little-studied plasmid related to Klebsiella spp. Conclusions: Our results reveal a new acquisition event of blaKPC in P. aeruginosa, in this case blaKPC-3. Likewise, the pandemic high-risk clones ST111 and ST235 of P. aeruginosa continues to spread blaKPC gene through different mobile genetic elements, jumping of conventional Tn4401b and acquiring new Tn2-derived NTE, which were inserted in diverse plasmids.